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Record W2112321133 · doi:10.1371/journal.pgen.1003270

ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

2013· article· en· W2112321133 on OpenAlexaff
Juliette Faraco, Ling Lin, Birgitte Rahbek Kornum, Eimear E. Kenny, Gosia Trynka, Mali Einen, Tom Rico, Peter Lichtner, Yves Dauvilliers, Isabelle Arnulf, Michel Lecendreux, Sirous Javidi, Peter Geisler, Geert Mayer, Fabio Pizza, Francesca Poli, Giuseppe Plazzi, Sebastiaan Overeem, Gert Jan Lammers, David Kemlink, Karel Šonka, Soňa Nevšímalová, Guy A. Rouleau, Alex Désautels, Jacques Montplaisir, Birgit Frauscher, Laura Ehrmann, Birgit Högl, Poul Jennum, Patrice Bourgin, Rosa Peraita‐Adrados, Álex Iranzo, Claudio L. Bassetti, Wei‐Min Chen, Patrick Concannon, Susan D. Thompson, Vincent Damotte, Bertrand Fontaine, Maxime Bréban, Christian Gieger, Norman Klopp, Panos Deloukas, Cisca Wijmenga, Joachim Hallmayer, Suna Önengüt-Gümüşcü, Stephen S. Rich, Juliane Winkelmann, Emmanuel Mignot

Bibliographic record

VenuePLoS Genetics · 2013
Typearticle
Languageen
FieldNeuroscience
TopicSleep and Wakefulness Research
Canadian institutionsCanadian Sleep & Circadian NetworkHôpital du Sacré-Cœur de MontréalUniversité de Montréal
FundersUCB PharmaNational Institute of Child Health and Human DevelopmentNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Allergy and Infectious DiseasesMedical Research CouncilWellcome TrustAgence Nationale de la RechercheNational Human Genome Research InstituteMünchner Zentrum für GesundheitswissenschaftenNational Institute of Neurological Disorders and StrokeBundesministerium für Bildung und ForschungInstitut National de la Santé et de la Recherche MédicaleNational Institutes of HealthFondation pour l'Aide à la Recherche sur la Sclérose en PlaquesCincinnati Children's Hospital Medical CenterJuvenile Diabetes Research Foundation International
KeywordsNarcolepsyBiologyImmunologyHuman leukocyte antigenMajor histocompatibility complexGeneticsT-cell receptorAntigenT cellImmune systemNeuroscienceNeurology

Abstract

fetched live from OpenAlex

Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.066
GPT teacher head0.326
Teacher spread0.260 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations246
Published2013
Admission routes1
Has abstractyes

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